Linezolid [(S)—N—[[3-(3-Fluoro-4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl] acetamide] is an antimicrobial agent. Linezolid is an oxazolidinone, having the empirical formula C16H20FN3O4 and the following structure (I):

Linezolid is described in The Merck Index (13th edition, Monograph number: 05526, CAS Registry Number: 165800-03-3) as white crystals, with a melting point of 181.5-182.5° C. Linezolid, as well as a process for its preparation, is disclosed in U.S. Pat. No. 5,688,792 (Example 5), European Patent No. 717738, Israeli Patent No. 110,802, Canadian Patent No. 2,168,560, and International Patent Publication WO 95/07271.
This oxazolidinone is marketed in the United States by Pfizer, Inc. as an injection, tablet, and oral suspension under the name ZYVOX®. It is mainly used to treat nosocomial pneumonia, skin and skin-structure infections, and vancomycin-resistant Enterococcus faecium infections.
U.S. Pat. No. 5,688,792, hereinafter the '792 patent, claims linezolid and its use for the treatment of microbial infections. This patent also discloses, but does not claim, the following method of preparation:

This method of preparation was also disclosed in Bricker, et al., J. Med. Chem., 39 673-679 (1996), where it was stated that the above route avoids the use of phosgene to make the carbamate precursor of the oxazolidinone ring. The authors also disclose that the use of NaN3 can be avoided by using potassium phthalimide, followed by deblocking of the phthalimide with aqueous methyl amine.
In the above-described synthesis, the intermediate amine, S—N-(4-morpholinyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl amine, having the following structure (II):
is reacted without isolation with acetic anhydride as an oily product or in solution to produce the acetamide, linezolid (I). This is followed by procedures for isolating the linezolid such as those described in the '792 patent (col. 15, 11. 22-28) wherein a method of chromatography and separation of the desired fraction is described, followed by evaporation and trituration of the product to obtain pure linezolid. Due to the necessary treatment required for recovery, linezolid is derived in low yields.
In the above-described syntheses, the intermediate azide, R—N-(4-morpholinyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl azide (III)
is reduced to its corresponding amine, S—N-(4-morpholinyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl-methyl amine (II) through catalytic hydrogenation in the presence of a palladium/carbon catalyst in the solvent ethyl acetate. These reaction conditions lead to the production of an undesirable level of reaction by-products, and thereby, following the acetylation of the intermediate amine (II) to linezolid (I), to undesirably high levels of bis-linezolid (IV).

It would be desirable to have a simple, efficient, industrial process for producing pure intermediate amine (II) used to then prepare linezolid (I) without the need of applying complicated and time consuming purification treatments, such as column chromatography, before the last trituration or recrystallization. The present invention provides such a method.